Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 44-54, 57-73 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The rejected claims cover methods of treating with platinum-based antineoplastic drugs.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”).
With regard to the recited genus of platinum-based antineoplastic drugs, the following applies:
Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010) states that “...a generic claim may define the boundaries of a vast genus of chemical compounds...the question may still remain whether the specification, including the original claim language, demonstrates that the applicant invented species sufficient to support a claim to a genus”. See page 1171.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
See also Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a “laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species.
Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) states that “it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it”.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or structural features common to the members of the genus, which features constitute a substantial portion of the genus, so that one of skill in the art can “visualize or recognize” the members of the genus (Emphasis added). Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(i), the court states, "An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention."
Courts have stated that “[i]n claims involving [non-genetic] chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). (emphasis added).
There is no such specificity here, nor could one skilled in the art identify any particular platinum-based antineoplastic drugs encompassed by the claims. Specifically, Applicant fails to disclose any other drugs, besides those specifically identified by the specification and claims, and in relation to the above, these disclosed species do not represent the substantial variety covered by the genus of platinum-based antineoplastic drugs.
With regard to the functional definition of platinum-based antineoplastic drugs, the specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116) because the specification contains almost no information by which a person of ordinary skill in the art would understand that the inventors possessed the all of the recited compounds. At best, it simply indicates that one should test an inordinate number of compounds to see if the compounds can perform the required function. In this connection, the specification contains no generic structural characteristics of those compounds which are platinum-based antineoplastic drugs, besides those compounds instantly disclosed, see In re ’318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”).
The Examiner acknowledges that a working example or exemplified embodiment is not necessarily a requirement for description. However, where a generic claim term is present in a claim, as in the present application, and defined only by functional characteristics, the specification must convey enough information, e.g., via sufficient representative examples, to indicate invention of species sufficient to constitute the genus. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 967 2 (Fed. Cir. 2002). The written description requirement “requires a description of an invention, not an indication of a result that one might achieve if one made that invention.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997); see also Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1350 (Fed. Cir. 2013) (“A patent...‘is not a reward for the search, but compensation for its successful conclusion.’ ... For that reason, the written description requirement prohibits a patentee from ‘leaving it to the ... industry to complete an unfinished invention.’” (citations omitted)).
Accordingly, the specification lacks adequate written description for the recited platinum-based antineoplastic drugs.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 44-73 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 20170240525 based on an application from PMV Pharmaceuticals, Inc. (PMV) or WO 2021061643, as evidenced by counterpart U.S. Publication No. 20220315564 based on an application by Binh et al. (Binh), in view of:
Mohell et al., Cell Death and Disease (2015) 6, e1794 (Mohell); and
Kupryjanczyk et al., BMC Cancer. 2008 Jan 29; 8:27 (Kupryjanczyk).
PMV discloses a method of treating a cancer in a subject in need thereof (method of increasing p53 mutant activity and treating a cancer by inducing apoptosis; paragraphs (0021], (0023], (0076]), the method comprising: I administering to the subject a therapeutically-effective amount of a compound that increases anticancer activity of a mutant p53 protein in the subject (method of increasing p53 mutant activity and treating a cancer by administering to a subject in need thereof a therapeutically-effective amount of a compound that binds a p53 mutant and increases the ability of the p53 mutant to bind DNA as compared to the ability of the p53 mutant to bind DNA; paragraphs (0021], [0023]):
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PMV discloses also administering to the subject a therapeutically-effective amount of an anti-cancer agent that functions through a pathway other than p53-induced apoptosis (the compound is administered in combination with another therapeutic agent, pharmaceutical compositions can be administered in conjunction with other therapies including chemotherapy, pharmaceutical compositions can be administered in therapeutically-effective amounts; paragraphs (0130], (0147]. [0151]).
PMV further discloses wherein the compound binds to the mutant p53 protein and reconforms the mutant p53 protein (compound binds a p53 mutant and increases the ability of the p53 mutant to bind DNA, the compound induces a conformational change in the p53 mutant; paragraphs (0023], (0983]) to a conformation of p53 that exhibits anti-cancer activity (the compound induces a conformational change in the p53 mutant and increases the stability of a biologically-active conformation of the p53 mutant, the restoration of activity of the p53 mutant leads to inhibition of cancer progression; paragraphs (0058], (0983], (1000]).
PMV further discloses wherein the compound increases a stability of the mutant p53 protein (the compound increases the stability of a biologically-active conformation of the p53 mutant; paragraph (1000]).
PMV further discloses wherein the cancer expresses the mutant p53 protein (method of inducing apoptosis in a cancer cell that expresses the p53 mutant by contacting the cell with compound; paragraphs (0022], (0076]). In this manner, treating the specific cancers recited in the claims is prima facie obvious.
PMV further discloses wherein the mutant p53 protein has a mutation at amino acid 220 (a compound selectively binds to the p53 Y220C mutant; paragraph (0068]).
PMV further discloses wherein the mutant p53 protein is p53 Y220C (a compound selectively binds to the p53 Y220C mutant; paragraph (0068]).
PMV further discloses wherein the compound selectively binds the mutant p53 protein as compared to a wild type p53 (a compound selectively. binds to the p53 Y220C mutant; paragraph (0068]).
PMV further discloses wherein the cancer is ovarian cancer (the condition is ovarian cancer; paragraphs [0989], (1006]).
PMV further discloses wherein the administering of the compound is oral (for oral administration, pharmaceutical compositions can be formulated; paragraph [0132]).
PMV further discloses wherein the therapeutically-effective amount of the compound (administering to a subject in need thereof a therapeutically-effective amount of a compound; paragraphs (0021], (0023]) is from about 500 mg to about 2000 mg (a compound can be present in a composition from 1 to 2000 mg; paragraph (0159]).
PMV further discloses wherein the subject is human (the subject is human; paragraphs [0996], (1013]).
The difference between PMV and the claimed inventions is that PMV does not teach the invention with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, based on the above, PMV teaches the elements of the claimed invention with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Binh also teaches compounds and methods to recover wild-type function to p53 mutants. The disclosed compounds bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation:
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Binh exemplifies the recited compound (i.e., claim 67) at page 28:
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Binh also teaches that:
[0102] The compounds of the present invention can selectively bind to a p53 mutant and can recover wild-type activity of the p53 mutant including, for example, DNA binding function and activation of downstream targets involved in tumor suppression. In some embodiments, a compound of the invention selectively binds to the p53 Y220C mutant. The Y220C mutant is a temperature sensitive mutant, which binds to DNA at lower temperature and is denatured at body temperature. A compound of the invention can stabilize the Y220C mutant to reduce the likelihood of denaturation of the protein at body temperature.
[0110] A compound of the invention can be used, for example, to induce apoptosis, cell cycle arrest, or senescence in a cell. In some embodiments, the cell is a cancer cell. In some embodiments, the cell carries a mutation in p53.
[0373] A dose can be expressed in terms of an amount of the drug divided by the mass of the subject, for example, milligrams of drug per kilograms of subject body mass. A compound described herein can be present in a composition in a range of from about 1 mg to about 2000 mg; from about 100 mg to about 2000 mg; from about 10 mg to about 2000 mg; from about 5 mg to about 1000 mg, from about 10 mg to about 500 mg, from about 50 mg to about 250 mg, from about 100 mg to about 200 mg, from about 1 mg to about 50 mg, from about 50 mg to about 100 mg, from about 100 mg to about 150 mg, from about 150 mg to about 200 mg, from about 200 mg to about 250 mg, from about 250 mg to about 300 mg, from about 300 mg to about 350 mg, from about 350 mg to about 400 mg, from about 400 mg to about 450 mg, from about 450 mg to about 500 mg, from about 500 mg to about 550 mg, from about 550 mg to about 600 mg, from about 600 mg to about 650 mg, from about 650 mg to about 700 mg, from about 700 mg to about 750 mg, from about 750 mg to about 800 mg, from about 800 mg to about 850 mg, from about 850 mg to about 900 mg, from about 900 mg to about 950 mg, or from about 950 mg to about 1000 mg.
[0315] In some embodiments, disclosed herein is a method of treating a cancer, the method comprising administering to a subject in need thereof a therapeutically-effective amount of a compound of the disclosure. A compound of the invention can, for example, slow the proliferation of cancer cell lines, or kill cancer cells. Non-limiting examples of cancer that can be treated by a compound of the invention and recited by the rejected claims are taught.
The primary references may not explicitly teach the recited combination therapies. However, combination therapies of agents, such as cisplatin and compounds that recover wild-type p53 function (or deplete mutant forms) were known and designed to overcome chemoresistance and trigger cancer cell death.
See Mohell:
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Moreover, taxane-platinum therapy is particularly justified in patients with TP53(+) tumors. By combining taxane with p53-targeting agent restores tumor-suppressor pathways that would otherwise allow cancer cells to survive and proliferate despite treatment, see Kupryjanczyk:
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In this way, those of ordinary skill could have combined taxane or platinum-based drugs with the instant compounds in the manner required and in a predictable fashion for the purposes of treating cancer. As outlined above, PMV teaches methods of treating a cancer in a subject with the instant compounds that increase p53 mutant activity. The secondary references are added for the proposition these compounds are applicable to taxane or platinum-based therapies. Specifically, the secondary references teach that compounds that recover wild-type p53 function overcome chemoresistance and trigger cancer cell death in taxane or platinum-based therapies. In this manner, those of ordinary skill would have recognized that applying this known technique with compounds that recover wild-type p53 function, such as those taught by PMV, to taxane or platinum-based therapies, would have yielded predictable results. Accordingly, combining the instant compounds that increase p53 activity with taxane or platinum-based drugs for purposes of overcoming chemoresistance and trigger cancer cell death would have been prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646
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